Pediatric migraine is one of the five most prevalent childhood disorders in the USA, affecting more than 6 million children and adolescents, up to 10% and 28% of each group, respectively. Recent advances in migraine research have demonstrated the cortical dysfunction plays a primary role in the cascade of migraine. To measure these functional, cortical abnormalities in the brain, magnetoencephalography (MEG) may be used to detect and localize functional brain activation with high spatial and temporal resolutions. Importantly, high-frequency brain signals (HFBS, ~2,632 Hz) have recently been found in the human brain. MEG detection of HFBS provides capability far beyond the conventional methods for revealing subtle cortical dysfunction. We hypothesize that MEG can quantitatively and noninvasively assess cortical dysfunction for children with migraine during and between migraine attacks. This hypothesis is based on the following observations: (1) Cortical dysfunction can be quantified and localized with newly developed MEG methods. (2) Increased neuromagnetic activation in 65-150 Hz has been volumetrically localized in the supplementary motor cortex in children with migraine, and (3) Abnormalities of cortical excitability in migraine have been found by using low frequency brain signals (<40 Hz) and MEG. Recent reports have shown that migraine attacks can be treated and/or prevented by normalizing cortical excitability with transcranial magnetic stimulation (TMS), medications and other methods. Building on our experience in pediatric migraine and clinical applications of MEG for more than a decade, we propose to address the following specific aims: (1) Quantify the spatial and spectral alteration of motor cortex excitability in pediatric migraine during migraine attacks with MEG;(2) Determine the spatial, spectral, frequency and temporal abnormalities of movement-evoked magnetic fields (MEFs) between migraine attacks. MEG data will be digitized at 6,000 Hz. Abnormalities of cortical excitability in migraine will be determined by analyzing neuromagnetic spectral power in 0-3,000 Hz at source levels using wavelet-based beamformer. Since MEG has mainly been used in the study of brain activities in low-frequency ranges (<40 Hz) in migraine in adults, the study of the motor cortex excitability in pediatric migraine with neuromagnetic signals in 0-3,000 Hz is novel. Quantification of the cortical excitability with neuromagnetic spectral and frequency signatures is technically innovative. Although this proposal focuses on motor cortex, the same methodologies can be applied to evaluate other brain areas as well. If successful, abnormalities of cortical excitability can be noninvasively assessed and localized with MEG. Effective methods for treating and preventing migraine attacks may be possible by normalizing cortical excitability with TMS, medication and other methods. Given that HFBS are a new discovery and our MEG methodologies are novel, improved treatment and prevention solutions based on better understanding of the mechanisms of migraine may protect children with migraine from progressing into a chronic condition with significant disability. PUBLIC HEALTH RELEVANCE: Building on recent discoveries that cortical excitability plays a primary role in the cascade of migraine progression and that the brain generates high-frequency brain signals (~2,632 Hz), we propose to use new MEG technology to quantitatively assess cortical dysfunction during acute migraine. This will add significant depth to the scientific understanding of brain activity during migraines and, if successful, may lead to the effective treatment and prevention of migraine headaches through noninvasive normalization or maintenance of cortical excitability.